Abstract:
:A fluorescence-based, high-resolution imaging approach was used to visualize longitudinally the cellular events unfolding during T cell-mediated tumor destruction. The dynamic interplay of T cells, cancer cells, cancer antigen loss variants, and stromal cells-all color-coded in vivo-was analyzed in established, solid tumors that had developed behind windows implanted on the backs of mice. Events could be followed repeatedly within precisely the same tumor region-before, during and after adoptive T cell therapy-thereby enabling for the first time a longitudinal in vivo evaluation of protracted events, an analysis not possible with terminal imaging of surgically exposed tumors. T cell infiltration, stromal interactions, and vessel destruction, as well as the functional consequences thereof, including the elimination of cancer cells and cancer cell variants were studied. Minimal perivascular T cell infiltrates initiated vascular destruction inside the tumor mass eventually leading to macroscopic central tumor necrosis. Prolonged engagement of T cells with tumor antigen-crosspresenting stromal cells correlated with high IFNγ cytokine release and bystander elimination of antigen-negative cancer cells. The high-resolution, longitudinal, in vivo imaging approach described here will help to further a better mechanistic understanding of tumor eradication by T cells and other anti-cancer therapies.
journal_name
Oncoimmunologyjournal_title
Oncoimmunologyauthors
Schietinger A,Arina A,Liu RB,Wells S,Huang J,Engels B,Bindokas V,Bartkowiak T,Lee D,Herrmann A,Piston DW,Pittet MJ,Lin PC,Zal T,Schreiber Hdoi
10.4161/onci.26677subject
Has Abstractpub_date
2013-11-01 00:00:00pages
e26677issue
11eissn
2162-4011issn
2162-402Xpii
2013ONCOIMM0284journal_volume
2pub_type
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